NAM is the official provider of online scientific reporting for the
8th International AIDS Society Conference on HIV Pathogenesis, Treatment
and Prevention (IAS 2015), which will take place in Vancouver, Canada,
19th-22nd July 2015.

A two-drug combination of sofosbuvir and ledipasvir cured
94% of previously untreated patients with genotype 1 hepatitis C infection
after eight weeks, without the need for ribavirin, Gilead Sciences announced on
Wednesday.

The results released on 18 December come from one of three
trials of the combination, ION-3. Two other studies tested the combination for
longer periods and with both previously untreated and treatment-experienced patients, and
showed similarly high cure rates after 12 or 24 weeks of treatment, with or
without ribavirin.

Gilead Sciences said that the very high cure rates observed
in the studies mean that it will be possible to speed up registration plans for
the combination. The company now plans to submit a licensing application in the
first quarter of 2014, which means that the combination could receive marketing
approval in the United States in the final quarter of 2014.

Sofosbuvir, a nucleotide polymerase inhibitor recently
approved in the United States and European Union, was paired with ledipasvir, a
NS5a inhibitor, in three studies testing different durations of treatment in
various populations.

The ION-1 study compared 12 and 24 weeks of treatment with
sofosbuvir and ledipasvir, with and without ribavirin, in previously untreated
patients with genotype 1 infection. Approximately 15% had cirrhosis.

The ION-2 study compared 8, 12 and 24 weeks of treatment
with sofosbuvir and ledipasvir, with and without ribavirin, in treatment-experienced
patients with genotype 1 infection who had experienced failure of previous
triple therapy with pegylated interferon, ribavirin and a protease inhibitor. Approximately
20% had cirrhosis.

The ION-3 study compared 8 and 12 weeks of treatment with
sofosbuvir and ledipasvir without ribavirin, with 12 weeks of treatment with
sofosbuvir and ledipasvir with ribavirin. All patients in this study were
previously untreated and had genotype 1 infection. None had cirrhosis.

Results

Gilead released 8- and 12-week results of ION 1, 2 and 3.
24-week results of ION-1 will be released in the first quarter of 2014.

Study

Population

Treatment

Duration

SVR12

ION-1

Genotype 1

Treatment-naive

N = 865

SOF/LDV

12 weeks

97.7%

SOF/LDV + RBV

12 weeks

97.2%

SOF/LDV

24 weeks

Not available

SOF/LDV + RBV

24 weeks

Not available

ION-2

Genotype 1

Treatment-experienced

N = 440

SOF/LDV

12 weeks

93.6%

SOF/LDV + RBV

12 weeks

96.4%

SOF/LDV

24 weeks

99.1%

SOF/LDV + RBV

24 weeks

99.1%

ION-3

Genotype 1

Treatment-naïve

N = 647

SOF/LDV

8 weeks

94.0%

SOF/LDV + RBV

8 weeks

93.1%

SOF/LDV

12 weeks

95.4%

4.1% of study participants in the study arms released
to date failed to achieve SVR12. Of these, just over half (36 patients out of
62, or 2.4% of all participants, experienced virologic failure: 35 due
to relapse and only one patient due to on-treatment breakthrough (this patient
was non-adherent to therapy). Twenty-six patients (1.7%) were lost to
follow-up or withdrew consent.

A more detailed breakdown of performance of each regimen and
treatment duration in patients with cirrhosis will be reported at a future
scientific meeting.

Gilead Sciences said that the ribavirin-sparing combination
was better tolerated: anaemia, a common side-effect of ribavirin, was reported
in 9.2% of patients who received ribavirin, compared to 0.5% of patients who
received sofosbuvir and ledipasvir without ribavirin. The most frequent side
effects of sofosbuvir and ledipasvir were headache and fatigue.

The results of these studies will pose a significant
challenge to other developers of interferon-free combinations for the treatment
of hepatitis C. An eight-week treatment course with two drugs will compare
favourably in the eyes of many patients and physicians to a longer duration of
treatment, although a major US pharmaceutical benefits company, which
negotiates process on behalf of insurers and managed-care organisations has
warned that it may only pay for more expensive hepatitis C drugs if they are
more effective. Convenience of dosing may not be enough to justify a higher
price.

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